Gene-study, interesting

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Thursday, July 17, 2008

The Secrets of Anti-Aging Genes

A new study asks why some people stay healthy into old age.

By Singer

An ambitious plan to sequence 100 genes in 1,000 healthy old people

could shed light on genetic variations that insulate some people from

the ailments of aging, including heart disease, cancer, and diabetes,

allowing them to live a healthy life into their eighties and beyond.

Rather than focusing on genetic variations that increase risk for

disease, scientists plan to focus on genes that have previously been

linked to health and longevity.

In recent years, advances

<http://www.technologyreview.com/Biotech/19028/> in genetic screening

technologies have allowed scientists to start searching

<http://www.technologyreview.com/Biotech/17193/?a=f> the genome for

clues to healthy aging and a lengthy life span. That work has revealed

that the genomes of healthy old people are not blemish free. " These

people have genetic susceptibility markers for many serious diseases,

including cardiovascular disease, stroke, and diabetes, but they don't

get any of these diseases, " says Topol

<http://www.scripps.edu/research/faculty.php?rec_id=23654> , a

cardiologist and head of the Genomic Medicine Program at the Scripps

Translational Science Institute, in La Jolla, CA, who is leading the

project. " What is the explanation? What might account for their

insulation from these diseases? "

To answer that question, researchers are collecting blood samples from

1,000 people age 80 or older who have never suffered any serious

illnesses and do not take medication. They plan to sequence 100 genes,

known from animal research and other studies to influence health and

aging. " We are especially interested in major housekeeping,

master-control genes like [those involved in] DNA repair or insulin

growth factor-1, " a protein hormone involved in cell growth, says Topol.

Enzymes involved in DNA repair are of interest in longevity research

because cells often accumulate mistakes in their DNA sequence with age,

and defects in some mouse and human DNArepairgenes trigger what looks

like premature aging. The receptor for insulin growth factor-1 (IGF1)

has been shown to affect aging in mice, nematodes, and flies.

Most previous studies have sequenced only a small number of genes or

used gene microarrays, which can quickly detect common genetic

variations throughout the genome. But recent research suggests that a

number of rarer variations in different genes play a role in health and

disease. Sequencing allows researchers to determine if healthy older

people are more likely to carry variations that either make protective

factors function more efficiently or hinder the activity of harmful

factors.

Topol and his collaborators will compare the gene sequences from the

healthy volunteers with DNA samples collected from people who died from

age-related diseases before they reached their eighties. The scientists

have already found that the healthy people had only a slightly lower

probability of carrying disease-linked variations. That supports the

idea that protective genes are playing a major role in people's

successful aging.

Scientists hope that identifying the molecular basis for this protective

effect will enable them to mimic it with drugs. " We believe longevity

genes are protecting against several age-related diseases rather than

just one, " says Nir Barzilai

<http://www.aecom.yu.edu/home/longevitygenesproject/staff.htm> , head of

the Longevity Genes Project at Albert Einstein College of Medicine, in

New York, who is not involved in the Scripps study. " From a

pharmaceutical perspective, it would be more cost effective to target

these pathways, and it would really imitate exceptional longevity rather

than just treating the diseases themselves. "

Barzilai has already identified a couple of candidates for longevity

genes. In an ongoing study

<http://www.technologyreview.com/Biotech/17949/> of people of Ashkenazi

Jewish descent age 95 or older, Barzilai and his colleagues showed that

the elderly group was more likely to carry a gene variant that changes

the way that people process cholesterol. More recently, the scientists

sequenced the genes for IGF1 and its receptor and found mutations unique

to female centenarians.

While Barzilai is taking a different approach to the gene hunt--using

microarrays--he says that each group looks forward to learning what the

other finds. Having two large studies of the genetics of healthy aging

will allow each to confirm its findings in a second population--a

crucial test of the validity of large-scale genomic studies.

Copyright Technology Review 2008.

S. Kalman PhD, RD, CCRC, FACN

Miami Research Associates

Director, Nutrition & Applied Clinical Research

6141 Sunset Drive #301

Miami, FL. 33143

(fax)

www.miamiresearch.com <http://www.miamiresearch.com>